Thao Dang, MD

Notch3 signaling pathway in human epithelial tumors

The goal of our funded research is to study the Notch3 signaling
pathway in human epithelial tumors, with a major interest in lung
cancer. In particular, we seek to understand the relationship between
Notch signaling and oncogenic processes such as apoptosis,
differentiation and metastasis. We also explore how Notch signaling
crosstalks with other growth factor pathways in oncogenesis. Our long
term goal is to use this information for [1] the better
characterization and understanding of clinical lung cancer syndromes,
and [2] develop and test molecular-based rational treatment concepts
against human lung carcinoma.

Recent data from our laboratory and others indicate that
overexpression of Notch3 is observed in many epithelial tumors.
Furthermore, Notch3 upregulates a number of anti-apoptosis pathways
leading to enhanced cancer cell survival. Inhibition of Notch3 by
pharmacological or genetic means results in growth arrest and/or tumor
cell death. Our work has also demonstrated significant crosstalk
between Notch3 and EGFR signaling. This observation suggests that
targeting multiple pathways in addition to Notch would yield higher
tumor cytotoxicity. As part of our translational goal, we focus on
developing strategies, such as monoclonal antibodies or recombinant
proteins, to target Notch signaling either alone or in combination with
other targeted therapies in preclinical and potential clinical
studies.